Age Related Maculopathy (ARM) is the leading cause of vision loss in the elderly population in the United States and Western world and is a major public health issue. Epidemiologic studies have indicated that heredity is a significant risk factor and family studies have further substantiated that ARM can be inherited as a dominant disease with late age of onset and variable expressivity. ARM is not well suited for traditional genetic investigations due to difficulties of clinical ascertainment and the small pedigrees because of its late onset. However, nonparametric linkage methods including Affected Pedigree Member method and simIBD provide a means of determining genetic loci that contribute to ARM susceptibility using small and intermediate-sized families. In our previous project we ascertained over 200 ARM families and are in the process of completing a candidate locus screening as well as a genome-wide scan of the first 120 families with 161 autosomal markers (average spacing of 20 cM). We have established a classification system that allows us to evaluate a stringently defined ARM population as well as larger sets of patients with less severe and/or ambiguous phenotypes. Several markers used in the initial candidate gene screening and chromosome-wide panels have provided results that suggest linkage with ARM. These will be investigated during the next grant period. We are proposing to expand our recruitment of ARM families to 1000 families and pursue a combination of genome-wide scans (200 and 350 families) with 10 cM resolution and focused genotyping based upon the tentative positively linked loci determined during the first grant period. The large number of families is necessary to confirm and further resolve potential ARM loci so that we can undertake candidate gene screening of our ARM population. The families that are not used in the genome-wide scans will be used for the focused genotyping effort, in the candidate gene screening program, and for disequilibrium linkage studies.